Preventing cancer by targeting abnormally expressed self-antigens: MUC1 vaccines for prevention of epithelial adenocarcinomas

摘要

Prophylactic vaccines basedontumor-associated antigens (TAAs) have elicited concerns due to theirpotential toxicity. Because TAAs are considered self-antigens, the prediction is that such vaccines will induce autoimmunity.While this has been observed in melanoma, where an antitumor immune response leads to vitiligo, autoimmunity has almost never been seen following vaccination with numerous other TAAs.We hypothesized that antigen choice determines outcome and have been working to identify TAAs whose expression differs between normal and tumor tissue, and thus could elicit antitumor immunitywithout autoimmunity. Studies on the epithelial TAAMUC1have revealed that, compared toMUC1on normal cells, tumors, premalignant lesions, and noncancerous pathologies affecting epithelial cells express abnormal MUC1, which is not a self-antigen but rather an abnormal disease-associated antigen (DAA). This distinction, which can be made for many known TAAs, has broad implications for the design and acceptance of preventative cancer vaccines.